The impact of antenatal and postnatal indoor air pollution or tobacco smoke exposure on lung function at 3 years in an African birth cohort.

BACKGROUND AND OBJECTIVE: Indoor air pollution (IAP) and tobacco smoke exposure (ETS) are global health concerns contributing to the burden of childhood respiratory disease. Studies assessing the effects of IAP and ETS in preschool children are limited. We assessed the impact of antenatal and postnatal IAP and ETS exposure on lung function in a South African birth cohort, the Drakenstein Child Health Study. METHODS: Antenatally enrolled mother-child pairs were followed from birth. Lung function measurements (oscillometry, multiple breath washout and tidal breathing) were performed at 6 weeks and 3 years. Quantitative antenatal and postnatal IAP (particulate matter [PM10 ], volatile organic compounds [VOC]) and ETS exposures were measured. Linear regression models explored the effects of antenatal and postnatal exposures on lung function at 3 years. RESULTS: Five hundred eighty-four children had successful lung function testing, mean (SD) age of 37.3 (0.7) months. Exposure to antenatal PM10 was associated with a decreased lung clearance index (p < 0.01) and postnatally an increase in the difference between resistance at end expiration (ReE) and inspiration (p = 0.05) and decrease in tidal volume (p = 0.06). Exposure to antenatal VOC was associated with an increase in functional residual capacity (p = 0.04) and a decrease in time of expiration over total breath time (tE /tTOT ) (p = 0.03) and postnatally an increase in respiratory rate (p = 0.05). High ETS exposure postnatally was associated with an increase in ReE (p = 0.03). CONCLUSION: Antenatal and postnatal IAP and ETS exposures were associated with impairment in lung function at 3 years. Strengthened efforts to reduce IAP and ETS exposure are needed.

Model validation for a knowledge and practices survey towards prevention of soil-transmitted helminth infections in rural villages in Indonesia.

The rate of soil-transmitted helminth (STH) infection is estimated to be around 20% in Indonesia. Health promotion and health education are cost-effective strategies to supplement STH prevention and control programs. Existing studies suggest that quantitative tools for knowledge, attitudes and practices (KAP) are important to monitor effective community-based STH interventions. However, evidence is limited regarding the applicability of such tools. This study aims to identify the socio-demographic predictors for STH-related knowledge and practices and validate the quantitative tools in population use. A cross-sectional study design was conducted among residents of 16 villages in Central Java, Indonesia. Adult and child respondents were interviewed to assess general knowledge and practices in relation to STH. Two mixed effects models identified the significant factors in predicting knowledge and practice scores. The model predicted knowledge and practice scores were compared with the observed scores to validate the quantitative measurements developed in this study. Participants' socio-demographic variables were significant in predicting an individual's STH-related knowledge level and their hand washing and hygiene practices, taking into account household-level variability. Model validation results confirmed that the quantitative measurement tools were suitable for assessing STH associated knowledge and behaviour. The questionnaire developed in this study can be used to support school- and community-based health education interventions to maximize the effect of STH prevention and control programs.

Position statement for adult and paediatric spirometry in South Africa: 2022 update.

Spirometry is required as part of the comprehensive evaluation of both adult and paediatric individuals with suspected or confirmed respiratory diseases and occupational assessments. It is used in the categorisation of impairment, grading of severity, assessment of potential progression and response to interventions. Guidelines for spirometry in South Africa are required to improve the quality, standardisation and usefulness in local respiratory practice. The broad principles of spirometry have remained largely unchanged from previous versions of the South African Spirometry Guidelines; however, minor adjustments have been incorporated from more comprehensive international guidelines, including adoption of the Global Lung Function Initiative 2012 (GLI 2012) spirometry reference equations for the South African population. All equipment should have proof of validation regarding resolution and consistency of the system. Daily calibration must be performed, and equipment quality control processes adhered to. It is important to have standard operating procedures to ensure consistency and quality and, additionally, strict infection control as highlighted during the COVID-19 pandemic. Adequate spirometry relies on a competent, trained operator, accurate equipment, standardised operating procedures, quality control and patient co-operation. All manoeuvres must be performed strictly according to guidelines, and strict quality assurance methods should be in place, including acceptability criteria (for any given effort) and repeatability (between efforts). Results must be categorised and graded according to current guidelines, taking into consideration the indication for the test.

Early evidence for historical overfishing in the Gulf of Mexico.

Fisheries encompass complex interplays between social, economic, and environmental factors, but limitations on historical fisheries data can hamper efforts to identify and contextualize the long-term spatiotemporal patterns that shape them. We integrate 2500 years of stable isotope (δ34S, δ13C, and δ15N) and zooarchaeological evidence from Gulf of Mexico fisheries to assess cultural, demographic, and technological changes affecting sheepshead (Archosargus probatocephalus) populations and fishing practices in Louisiana, USA. Concurrent with human population growth, average sizes of sheepshead caught decreased from the 1720s to 1830s. The size of fish caught after the 1830s increased to pre-1720 levels at the same time that isotopic compositions of fish bone collagen show that fish were being caught from a more diverse range of ecosystems, including distant seagrass beds. Our findings provide the first evidence for large-scale depressions of historical sheepshead populations and the processes driving them, including rapid human population growth and sustained harvesting pressure.

Arterial Platelet Adhesion in Atherosclerosis-Prone Arteries of Obese, Insulin-Resistant Nonhuman Primates.

Background Platelet-endothelial interactions are thought to contribute to early atherogenesis. These interactions are potentiated by oxidative stress. We used in vivo molecular imaging to test the hypothesis that platelet-endothelial interactions occur at early stages of plaque development in obese, insulin-resistant nonhuman primates, and are suppressed by NADPH-oxidase-2 inhibition. Methods and Results Six adult rhesus macaques fed a Western-style diet for a median of 4.0 years were studied at baseline and after 8 weeks of therapy with the NADPH-oxidase-2-inhibitor apocynin (50 mg/kg per day). Six lean control animals were also studied. Measurements included intravenous glucose tolerance test, body composition by dual-energy X-ray absorptiometry, carotid intimal medial thickness, carotid artery contrast ultrasound molecular imaging for platelet GPIbα (glycoprotein- Ibα) and vascular cell adhesion molecule-1, and blood oxidative markers on mass spectrometry. Compared with lean controls, animals on a Western-style diet were obese (median body mass: 16.0 versus 8.7 kg, P=0.003; median truncal fat: 49% versus 20%, P=0.002), were insulin resistant (4-fold higher insulin-glucose area under the curve on intravenous glucose tolerance test, P=0.002), had 40% larger carotid intimal medial thickness (P=0.004), and exhibited oxidative signatures on proteomics. In obese but not lean animals, signal enhancement on molecular imaging was significantly elevated for GPIbα and vascular cell adhesion molecule-1. The signal correlated modestly with intimal medial thickness but not with the degree of insulin resistance. Apocynin significantly (P<0.01) reduced median signal for GPIbα by >80% and vascular cell adhesion molecule-1 signal by 75%, but did not affect intimal medial thickness, body mass, or intravenous glucose tolerance test results. Conclusion In nonhuman primates, diet-induced obesity and insulin resistance leads to platelet-endothelial adhesion at early atherosclerotic lesion sites, which is associated with the expression of pro-inflammatory adhesion molecules. These responses appear to be mediated, in part, through oxidative pathways.

Aetiology and presentation of childhood pleural infections in the post-pneumococcal conjugate vaccine era in South Africa.

Background: Complications of respiratory infections including pleural effusion (PE) are associated with a high morbidity. Differentiating between PE caused by Mycobacterium tuberculosis (Mtb) infection and other bacterial infections in endemic areas is difficult in children, thus, impacting treatment. Objectives: To investigate the aetiology of PE and features distinguishing tuberculosis (TB) from bacterial PE in children. Methods: We conducted a prospective study in children with PE admitted to a tertiary hospital in Cape Town from December 2017 to December 2019. Clinical information and routine laboratory investigations were compared between children with bacterial, Mtb or unclassified PE, categorised according to study definitions. Results: A total of 91 patients were included in the present study and their median age was 31 months (interquartile range (IQR) 11.8 - 102.1). The aetiology was bacterial in 40% (n=37), Mtb in 39% (n=36) and unclassified in 20% (n=18) of patients. Staphylococcus aureus was the most common bacterial isolate, confirmed in 65% (n=24/37) patients, and Streptococcus pneumoniae was confirmed in only 8% of patients. TB was microbiologically confirmed in 33% (n=12/36) of patients. Patients with TB were older (91.6 v. 11.8 months; p<0.001), with more weight loss (28 v. 12 patients; p<0.001), and longer cough duration (10 v. 4 days; p<0.001) than those with other bacterial PE. In contrast, the latter had significantly higher serum C-reactive protein (median 250 v. 122 mg/L; p<0.001), procalcitonin (11 v. 0.5 mg/L; p<0.001), pleural fluid lactate dehydrogenase (7 280 v. 544 U/L; p<0.001), and adenosine deaminase levels (162 v. 48 U/L; p<0.001) and lower glucose levels (1.3 v. 4 mmol/L; p<0.001). Conclusion: Post 13-valent pneumococcal conjugate vaccine, S. aureus is the dominant cause of PE in children using traditional culture methods, while Mtb remains a common cause of PE in our setting. Useful clinical and laboratory differences between Mtb and other bacterial PE were identified, but the cause of PE in 20% of children was underdetermined. Molecular testing of pleural fluid for respiratory pathogens may be useful in such children.

Post-tuberculosis lung health: perspectives from the First International Symposium.

ALTHOUGH CURABLE, TB frequently leaves the individual with chronic physical and psycho-social impairment, but these consequences have been largely neglected. The 1st International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to discuss priorities and gaps in addressing this issue. A barrier to progress has been the varied terminology and nomenclature, so the Delphi process was used to achieve consensus on definitions. Lack of sufficient evidence hampered definitive recommendations in most domains, including prevention and treatment of post-TB lung disease (PTLD), but the discussions clarified the research needed. A consensus was reached on a toolkit for future PTLD measurement and on PTLD patterns to be considered. The importance of extra-pulmonary consequences and progressive impairment throughout the life-course was identified, including TB recurrence and increased mortality. Patient advocates emphasised the need to address the psychological and social impacts post TB and called for clinical guidance. More generally, there is an urgent need for increased awareness and research into post-TB complications.

Tandem P-selectin glycoprotein ligand immunoglobulin prevents lung vaso-occlusion in sickle cell disease mice.

Sickle cell disease (SCD) is a monogenic disorder estimated to affect more than three million people worldwide. Acute systemic painful vaso-occlusive episode (VOE) is the primary reason for emergency medical care among SCD patients. VOE may also progress to acute chest syndrome (ACS), a type of acute lung injury and one of the primary reasons for mortality among SCD patients. Recently, P-selectin monoclonal antibodies were found to attenuate VOE in SCD patients and lung vaso-occlusion in transgenic humanized SCD mice, highlighting the therapeutic benefit of P-selectin inhibition in SCD. Here, we use quantitative fluorescence intravital lung microscopy (qFILM) to illustrate that tandem P-selectin-glycoprotein ligand-immunoglobulin (TSGL-Ig) fusion molecule containing four P-selectin binding sites, significantly attenuated intravenous (IV) oxyhemoglobin triggered lung vaso-occlusion in SCD mice. These findings highlight the therapeutic potential of TSGL-Ig in preventing VOE and ACS in SCD.

The Standardization of Outpatient Procedure (STOP) Narcotics after anorectal surgery: a prospective non-inferiority study to reduce opioid use.

BACKGROUND: Prescription of opioid medication after ambulatory anorectal surgery may be excessive and lead to opioid misuse. The purpose of this study was to evaluate the efficacy of a multi-modality opioid-sparing approach to control postoperative pain and reduce opioid prescriptions after outpatient anorectal surgery. METHODS: A prospective non-inferiority pre- and post-intervention study was completed at three academic hospitals. Patients included were 18-75 years of age who had outpatient anorectal surgeries. The Standardization of Outpatient Procedure (STOP) Narcotics intervention was implemented, which is a multi-pronged analgesia bundle integrating patient education, health care provider education, and intra-/postoperative analgesia focused on multi-modal pain control strategies and opioid-reduced prescriptions. The primary outcome was patient-reported average pain in the first 7 postoperative days. Secondary outcomes included patient-reported quality of pain management, medication utilization, prescription refills and medication disposal. RESULTS: Ninety-three patients had outpatient anorectal surgery (42 pre-intervention and 51 post-intervention). No difference was seen in average postoperative pain in the pre- vs. post-intervention groups (2.8 vs. 2.6 on an 11-point scale, p = 0.33) or patient-reported quality of pain control (good/very good in 57% vs. 63%, p = 0.58). The median oral morphine equivalents (OME) prescribed was significantly less [112.5 (IQR 50-150) pre-intervention vs. 50 (IQR 50-50) post-intervention, p < 0.001]. In the post-intervention group, only 45% of patients filled their opioid prescription and median opioid use was 12.5 OME (2.5 pills). CONCLUSIONS: While pain control after anorectal surgery must consider the individual patient's needs, a standardized pain care bundle significantly decreased opioid prescribing without an increase in patient-reported postoperative pain.

An urgent need for African spirometry reference equations: the Paediatric and Adult African Spirometry study.

BACKGROUND: The GLI2012 (Global Lung Initiative 2012) has provided the largest data set to date for multi-ethnic spirometry reference equations; however, data on African populations are limited. In pulmonary function testing, diagnosis of lung disorder is based on comparing the individual's lung function to a reference appropriate for sex and ethnicity.METHODS: We conducted a systematic review of studies reporting spirometry results in healthy children and adults in Africa. Data from these studies were collated for Z-scores of forced expiratory volume in 1 sec (zFEV1), forced vital capacity (zFVC) and zFEV1/FVC compared to GLI reference equations.RESULTS: Nine studies, covering a total of 4750 individuals from North, South, East, West and Central Africa (52% were female), were reviewed. Marked differences were noted between individuals from North Africa and sub-Saharan Africa. The Southern zFEV1 (-0.12 ± 0.98), zFVC (-0.15 ± 0.98) and zFEV1/FVC (0.05 ± 0.89), Central zFEV1 (-0.16 ± 0.79), zFVC (-0.09 ± 0.83) and zFEV1/FVC (-0.17 ± 0.71) and East African zFEV1 (0.10 ± 0.88), zFVC (0.16 ± 0.85) and zFEV1/FVC (-0.10 ± 0.95) cohorts had an excellent fit with the GLI-African American. The West African showed a poor fit to all reference equations. The North African group showed the best fit for the GLI Caucasian zFEV1 (-0.12 ± 1.37), zFVC (-0.26 ± 1.36) and zFEV1/FVC (0.25 ± 1.11). The zFEV1/FVC ratios were stable across all the populations.CONCLUSION: Current evidence seems to support the use of GLI2012 reference values in North African and sub-Saharan African populations after taking into account ethnic correction factors.

Similarities and differences in the biotransformation and transcriptomic responses of Caenorhabditis elegans and Haemonchus contortus to five different benzimidazole drugs.

We have undertaken a detailed analysis of the biotransformation of five of the most therapeutically important benzimidazole anthelmintics - albendazole (ABZ), mebendazole (MBZ), thiabendazole (TBZ), oxfendazole (OxBZ) and fenbendazole (FBZ) - in Caenorhabditis elegans and the ruminant parasite Haemonchus contortus. Drug metabolites were detected by LC-MS/MS analysis in supernatants of C. elegans cultures with a hexose conjugate, most likely glucose, dominating for all five drugs. This work adds to a growing body of evidence that glucose conjugation is a major pathway of xenobiotic metabolism in nematodes and may be a target for enhancement of anthelmintic potency. Consistent with this, we found that biotransformation of albendazole by C. elegans reduced drug potency. Glucose metabolite production by C. elegans was reduced in the presence of the pharmacological inhibitor chrysin suggesting that UDP-glucuronosyl/glucosyl transferase (UGT) enzymes may catalyze benzimidazole glucosidation. Similar glucoside metabolites were detected following ex vivo culture of adult Haemonchus contortus. As a step towards identifying nematode enzymes potentially responsible for benzimidazole biotransformation, we characterised the transcriptomic response to each of the benzimidazole drugs using the C. elegans resistant strain CB3474 ben-1(e1880)III. In the case of albendazole, mebendazole, thiabendazole, and oxfendazole the shared transcriptomic response was dominated by the up-regulation of classical xenobiotic response genes including a shared group of UGT enzymes (ugt-14/25/33/34/37/41/8/9). In the case of fenbendazole, a much greater number of genes were up-regulated, as well as developmental and brood size effects suggesting the presence of secondary drug targets in addition to BEN-1. The transcriptional xenobiotic response of a multiply resistant H. contortus strain UGA/2004 was essentially undetectable in the adult stage but present in the L3 infective stage, albeit more muted than C. elegans. This suggests that xenobiotic responses may be less efficient in stages of parasitic nematodes that reside in the host compared with the free-living stages.

Introduction of a mobile device based tertiary survey application reduces missed injuries: A multi-center prospective study.

BACKGROUND: Missed injuries during the initial assessment are a major cause of morbidity after trauma. The tertiary survey is a head-to-toe exam designed to identify any injuries missed after initial resuscitation. We designed a novel mobile device application (Physician Assist Trauma Software [PATS]) to standardize performance and documentation of the tertiary survey. This study was undertaken to assess the feasibility of introducing PATS into routine clinical practice, as well as its capacity to reduce missed injuries. METHODS: Prior to implementation of PATS, the missed injury rates at a higher-volume and a medium-volume level I trauma center were assessed. The PATS program was implemented simultaneously at both centers. Missed injuries were tracked during the study period. Compliance and tertiary survey completion rates were evaluated as a marker of feasibility. RESULTS: At the higher-volume trauma center, the missed injury rated decreased from 1% to 0% with the introduction of the PATS program (p = 0.04). At the medium-volume trauma center, the missed injury rate decreased from 9% to 1% (p < 0.001). Compliance and documentation increased from 68% to 100%, and from no formal documentation to 60% compliance at the higher- and medium-volume centers respectively. CONCLUSIONS: The implementation of a mobile tertiary survey application significantly reduced missed injuries at both a higher- and medium-volume trauma center. The use of this application resulted in a significant improvement in compliance with documentation of the tertiary survey.

Effect of temperature, oxygen and light on the degradation of ß-carotene, lutein and α-tocopherol in spray-dried spinach juice powder during storage.

The aim of this study was to evaluate the interaction between packaging parameters (transmission of light and oxygen) and storage temperatures (4, 20, 40 °C) on nutrient retention of Spinach (Spinacia oleracea) juice, spray-dried in the absence of an added encapsulant. ß-Carotene was more susceptible to degradation compared with lutein and α-tocopherol. Under our experimental conditions, it was observed that excluding low fluorescent light intensity and air by vacuum packaging at 20 °C did not seem to improve nutrient retention loss over time (p > 0.05). The rate of ß-carotene, lutein and α-tocopherol loss displayed first order reaction kinetic with low activation energy of 0.665, 2.650 and 13.893 kJ/mol for vacuum, and 1.089, 4.923 and 14.142 kJ/mol for non-vacuum, respectively. The reaction kinetics and half-life for ß-carotene, lutein and α-tocopherol at 4 °C and non-vacuumed were 2.2 × 10-2, 1.2 × 10-2, and 0.8 × 10-2 day-1, and 32.08, 58.25 and 85.37 day, respectively.

Internal Validation of RapidHIT® ID ACE Sample Cartridge and Assessment of the EXT Sample Cartridge*†.

A new rapid DNA solution, the RapidHIT® ID, can accommodate two different sample cartridges, ACE, for the analysis of a single swab and EXT, for the analysis of DNA extracts. An efficient internal validation designed for low-throughput rapid DNA is described. An evaluation of the EXT sample cartridge is also described. Each cartridge generated profiles with sufficient data quality to meet CODIS eligibility in fewer than 120 min. The results exhibited 100% correlation when compared to conventional DNA typing methods. Precision, reproducibility, stochastic, mixture, and contamination experiments produced expected results. Sensitivity of the ACE sample cartridge was acceptable for buccal swab analysis. The sensitivity of the EXT sample cartridge is discussed. The ACE validation and the EXT evaluation utilized a minimalist, cost-saving, efficient design to generate a validated RapidHIT® ID instrument capable of producing genetic profiles from both extracted forensic DNA samples and buccal swab samples within 120 min.

Genetic Modification of Grapevine Embryogenic Cultures.

Precision breeding is an approach to grapevine genetic improvement that transfers only specific traits among sexually compatible species via the relatively stable mitotic cell division pathway in order to avoid the significant disruption imposed upon conventional breeding by meiosis. Factors enabling precision breeding include the availability of the Vitis genome sequence combined with highly optimized gene insertion and plant regeneration protocols. A protocol for the production of grapevine embryogenic cultures and their genetic transformation is described. Embryogenic cultures are produced from either leaf or floral explants. Somatic embryos at the cotyledonary stage of development are used for Agrobacterium-mediated transformation. Following co-cultivation with Agrobacterium containing the genes of interest, modified embryos are selected on the basis of anthocyanin pigmentation and antibiotic resistance. Somatic embryos are then germinated to produce modified plants that are hardened and transferred to a greenhouse. The presence of the genes of interest is confirmed by PCR.

Point-of-care brain injury evaluation of conscious awareness: wide scale deployment of portable HCS EEG evaluation.

Survivors of severe brain injury may remain in a decreased state of conscious awareness for an extended period of time. Clinical scales are used to describe levels of consciousness but rely on behavioural responses, precipitating misdiagnosis. We have previously utilized event-related potentials (ERPs) to circumvent reliance on behavioural responses. However, practical implementation barriers limit the clinical utility of ERP assessment at point-of-care (POC). To address this challenge, we developed the Halifax Consciousness Scanner (HCS)-a rapid, semi-automated electroencephalography system. The current study evaluated: (i) HCS feasibility in sub-acute, POC settings nationwide; (ii) ERP P300 responses in patients with acquired brain injury versus healthy controls; and (iii) correlations within and between clinical measures and P300 latencies. We assessed 28 patients with severe, chronic impairments from brain injuries and contrasted the results with healthy control data (n = 100). Correlational analyses examined relationships between P300 latencies and the commonly used clinical scales. P300 latencies were significantly delayed in patients compared to healthy controls (P < 0.05). Clinical assessment scores were significantly inter-correlated and correlated significantly with P300 latencies (P < 0.05). In sub-acute and chronic care settings, the HCS provided a physiological measure of neurocognitive processing at POC for patients with severe acquired brain injury, including those with disorders of consciousness.

Hospital doctors' experiences of caring for dying patients.

BACKGROUND: The aim of this study was to examine, by means of a postal questionnaire, the experience of all grades of doctors caring for patients dying in an acute hospital in Scotland. METHOD: A postal questionnaire was sent to 306 doctors working in inpatient medical and surgical specialties, emergency medicine, anaesthetics and intensive care medicine in an acute hospital. RESULTS: There was an overall 41% response rate (127/306). Of responding doctors 55% had cared for 10 or more patients in the previous year. A quarter of respondents had personal experience of bereavement outside of clinical practice within the previous year. A total of 65% of responding doctors agreed that their most memorable patient death had had a strong emotional impact upon them. Responding doctors reported benefit from peer support. There was no association between length of time as a doctor and difficulty rating for talking to patients about death (p-value: 0.203). There was no association between difficulty rating and length of time working as a doctor when talking to relatives about death and dying (p-value: 0.205). We considered the questionnaire responses in relation to Scottish Government policy and initiatives associated with the care of the dying, and the future training and support of doctors caring for this group of patients and their relatives. CONCLUSION: Doctors describe similar experiences in terms of communication difficulties and emotional effects of caring for dying patients irrespective of their length of time working as a doctor.